From the top of the NFL to the bottom of the heap, teams are already feeling the pain.
Key performers are dropping like they've been through two months of the season, not two weeks. The latest: Adrian Peterson , Jimmy Garoppolo, DeMarcus Ware, Josh McCown , Danny Woodhead , Jonathan Stewart and Arian Foster.
The Patriots, perhaps the league's best team, appear to be down to their third QB. The Browns, possibly the NFL's worst team, are working on No. 3, rookie Cody Kessler.
Most worrisome, though, is Peterson, the 2012 league MVP and Minnesota's cornerstone on offense who has a torn meniscus in his right knee.
He has remarkable recovery skills — Peterson tore the ACL in his left knee in the second-to-last game of the 2011 season, then played all of 2012 and rushed for more than 2,000 yards. But this is four years later, it's the other knee and he was unable to put pressure on his leg as he hobbled off the field. Then Peterson needed help getting to the locker room.
He was on crutches after the game, wearing a brace on his right leg. Coach Mike Zimmer said Monday that the team is "exploring all options."
Usually, a torn meniscus requires several weeks of rehab before a player can return to the field.
Garoppolo hardly is a star, with two pro starts on his resume. But he sure was doing a nice imitation of Tom Brady while the four-time Super Bowl champion is serving his four-game "Deflategate" suspension.
Now Jimmy G's immediate future is in doubt after taking a monstrous hit from Miami linebacker Kiko Alonso on a second-quarter pass play. Garoppolo barely was able to move his shoulder as he walked off the field.
As usual, Patriots coach Bill Belichick isn't supplying much info on his third-year quarterback, saying only the team will take a day-to-day approach. Rookie Jacoby Brissett finished off the win.
"This game is a 100 percent injury rate," Patriots receiver Julian Edelman said. "It's football and everyone's just gotta do their job a little bit better."
Cleveland lost starting quarterback Robert Griffin III last week with a shoulder problem. Now McCown is plagued by the same kind of hurt, though he finished Sunday's 25-20 loss to Baltimore.
Unable to lift his left arm after the game, McCown said he planned to play next week at Miami. Sorry: On Monday, Browns coach Hue Jackson said the sprained shoulder meant Kessler would start instead of McCown at Miami.
"We'll find out a lot about him this weekend," Jackson said of Kessler, a third-round draftee in April.
Denver's superb defense isn't anchored by the 34-year-old Ware, but he's an important component. The linebacker/pass rush specialist broke his right forearm against Indianapolis and will require surgery Tuesday that will sideline him for four to five weeks.
Ware missed all but the final few days of training camp to protect his back, which kept him out of five games last season.
Losing Ware isn't a deal breaker for the Broncos, but the defending champions recognize their defense must stay strong and deep for them to contend again.
Of the three significant injuries to running backs, Woodhead's was the worst, a torn right ACL. The versatile Chargers sparkplug was taken off the sideline on a cart with an apparent right knee issue, and on Monday was placed on injured reserve.
In their opener, the Chargers lost top wideout Keenan Allen for the year. Philip Rivers could be without two of his most dependable sidekicks, although it's helped San Diego that 2015 first-round pick Melvin Gordon has emerged at running back.
Miami's Foster went down with a groin injury. He already was struggling with a hamstring issue and is coming off surgery to repair his Achilles tendon.
Stewart, Carolina's workhorse back, was hurt in the Super Bowl and it damaged the Panthers' attack in February. Although coach Ron Rivera claims his team is deep at the position, Stewart is a mainstay. If his hamstring injury is a major one, it's a blow to the NFC champs.
As Edelman said, injuries are unavoidable in pro football. Often, the healthiest team when winter hits winds up playing for and probably walking off with the Lombardi Trophy.
Most troubling, though, is when the injury bug hits so soon. Many a team's talented roster has been torn asunder by a lack of health, including Baltimore and Dallas a year ago. It's important, yet difficult, to avoid thinking that if September is so hurtful, what will the rest of the schedule be like?
But the approach has to be a positive one, even when untested quarterbacks are calling signals and Hall of Fame-caliber running backs are hobbled.